Efficacy of Nanoparticle Albumin-Bound Paclitaxel (nab-PTX) Monotherapy Can Be Improved after Treatment with Immune Checkpoint Inhibitor in Patients with Non-Small Cell Lung Cancer: Long-Term Follow-Up and Updated Analysis of Two Previous Prospective Clinical Studies.

INTRODUCTION: Recent studies have suggested enhanced therapeutic effects of subsequent chemotherapy after immune checkpoint inhibitor (ICI) treatment, highlighting the importance of subsequent treatment selection. Nanoparticle albumin-bound paclitaxel (nab-PTX) is commonly used in subsequent chemotherapies; however, its efficacy as a subsequent treatment after ICI treatment has not been reported. METHODS: We retrospectively evaluated the efficacy and safety of nab-PTX using two prospective studies that we previously reported. The first study evaluated the efficacy and safety of nab-PTX as a second-line treatment after the failure of the first-line cytotoxic chemotherapy, excluding ICI (study 1; n = 32), and the other as a subsequent treatment after failure of ICI treatment, regardless of treatment line (study 2; n = 29). RESULTS: The objective response rate was significantly higher in study 2 {55.2% (95% confidence interval [CI]: 28.1-79.6)} than in study 1 (28.1% [95% CI: 13.7-46.7]) (p = 0.04). Although the disease control rate was slightly higher in study 2 (86.2% [95% CI: 65.9-97.0]) than in study 1 (71.9% [95% CI: 53.3-86.3]), there was no significant difference (p = 0.2). The median progression-free survival was significantly longer in study 2 than in study 1 (3.9 months [95% CI: 2.0-5.5] in study 1 vs. 5.6 months [95% CI: 3.0-12.8] in study 2; hazard ratio [HR]: 0.46 [95% CI: 0.27-0.81], p = 0.006). The median overall survival was slightly longer in study 2 despite the greater number of patients who received nab-PTX in late treatment line, but there was no significant difference between study 1 and study 2 (10.9 months [95% CI: 5.1-16.8] in study 1 vs. 11.9 months [95% CI: 7.6-24.8] in study 2; HR: 0.77 [95% CI: 0.46-1.31], p = 0.34). Safety profiles did not differ between the patients in studies 1 and 2. CONCLUSION: Nab-PTX monotherapy may be an effective subsequent treatment option after ICI treatment.

Safety and utility of Endoscopic Ultrasound with Bronchoscope-guided Fine Needle Aspiration (EUS-B-FNA) in suspected lung cancer patients with poor respiratory or general conditions: a prospective three-center observational study.

BACKGROUND: Although transbronchial diagnostic procedures are sometimes difficult to perform because of the patient's respiratory or general conditions, endoscopic ultrasound with bronchoscope-guided fine-needle aspiration (EUS-B-FNA), a known transesophageal diagnostic procedure, might be useful for such cases. We conducted this prospective three-center observational study to evaluate the safety and efficacy of EUS-B-FNA in suspected lung cancer patients with poor respiratory or general conditions. METHODS: Patients with suspected lung cancer with respiratory failure, Eastern Cooperative Oncology Group performance status of 2 or higher, or severe respiratory symptoms, were enrolled. The primary endpoints were the diagnostic yield of lung cancer and its safety, and the secondary endpoints were the success rate of molecular and programmed death ligand 1 (PD-L1) analyses, and the 6-month survival rate in patients with lung cancer. RESULTS: We enrolled 30 patients, of which 29 were included in the analysis. Among them, 26 were eventually diagnosed with lung cancer. The diagnostic yield for lung cancer was 100% (26/26). There were no adverse events associated with EUS-B-FNA requiring procedure discontinuation. The success rates of molecular analysis for EGFR, ALK, ROS-1, and BRAF were 100% (14/14), 100% (11/11), 100% (9/9), and 75% (6/8), respectively. The success rate of the PD-L1 analysis was 100% (15/15). The 6-month survival rate in patients with lung cancer was 53.8% (95% confidence interval [CI]: 33.4-76.4), and the median overall survival (OS) was 196 days (95% CI: 142-446). CONCLUSIONS: EUS-B-FNA is a safe and effective diagnostic method, even in patients with suspected lung cancer with poor respiratory or general conditions. TRIAL REGISTRATION: This clinical trial was registered at https://www.umin.ac.jp/ctr/index.htm (UMIN000041235, approved on 28/07/2020).

Effect of oral tolvaptan for 1 year in patients with functional mitral regurgitation.

The effect of the oral selective vasopressin V2-receptor antagonist tolvaptan for chronic phase therapy on patients with FMR remains unclear. We aimed to determine the efficacy of oral tolvaptan in patients with significant functional mitral regurgitation (FMR) to reduce the mortality and rehospitalization due to worsening heart failure (HF). We enrolled 219 patients (mean age 76 ± 9 years, 59.4% men) who were admitted at our hospital due to congestive HF during different two 1-year periods. The patients were divided into 2 groups: those who had significant FMR (MR ≥ grade 2 [n = 76]) and those who did not (MR < grade 2 [n = 143]) at discharge. The patients were further divided into a study group that received tolvaptan during follow-up and a control group that did not receive tolvaptan. We used an inverse probability of treatment weighting method with the primary end point defined as overall all-cause mortality and rehospitalization due to worsening HF within 1 year. Of the 76 patients with significant FMR at discharge, 2 of 20 (10%) who were administered tolvaptan died and 8 (40%) were readmitted to a hospital. Of the 56 patients who did not receive tolvaptan, 2 (3.5%) died and 18 (27.5%) required rehospitalization. After multiple adjustments, there were no significant differences for overall survival and rehospitalization between the groups (log-rank p = 0.700 and 0.510, respectively). Our results suggest that oral tolvaptan administration in addition to conventional diuretics had less impact on outcomes in patients with significant FMR.

Increased risk of Legionella pneumonia as community-acquired pneumonia after heavy rainfall in 2018 in west Japan.

INTRODUCTION: Japan experienced a heavy rainfall event from June 28 to July 8, 2018, and many casualties were caused by both heavy rainfall and flooding. Few studies have investigated patients' characteristics and the causative pathogens of community-acquired pneumonia before and after heavy rainfall events. The aim of the present study was to evaluate the causative pathogens and clinical characteristics of hospitalized patients with community-acquired pneumonia before and after the heavy rainfall event using prospective cohort data. METHODS: The study was divided into two periods: July to November 2013-2017 (before heavy rainfall) and July to November 2018 (after heavy rainfall). The patients' clinical characteristics and causative pathogens before and after the heavy rainfall were investigated. Regarding the causative pathogens, adjustments were made for precipitation and seasonal patterns. RESULTS: There were no significant differences in the number and clinical characteristics of patients before and after heavy rainfall. However, the frequency of Legionella pneumonia was significantly higher after than before the heavy rainfall event (8.9% vs 3.0%, P = 0.02) and remained significant after adjusting for precipitation and season. Three of 7 Legionella pneumonia patients engaged in reconstruction work and 2 Legionella pneumonia patients had soil exposure. CONCLUSIONS: An increased risk of Legionella pneumonia after not only rainfall and serious flooding, but also following recovery work or soil exposure should be considered.

Clinical safety and efficacy of tolvaptan for acute phase therapy in patients with low-flow and normal-flow severe aortic stenosis.

Conventional diuretic therapy for low-flow (LF) severe aortic stenosis (SAS) often has an inadequate effect or causes hemodynamic instability. Tolvaptan is used for acute heart failure in addition to conventional diuretics, and it does not cause intravascular dehydration. This study aimed to retrospectively investigate the safety and efficacy of tolvaptan in the acute phase in 56 consecutive patients with SAS and compared LF-SAS with normal-flow (NF) SAS. The primary endpoints were adverse clinical events (death, worsening heart failure, worsening renal failure, fatal arrhythmia, cardiogenic or hypovolemic shock, and use of inotropic agents) and the volume of urine within 48 h of tolvaptan administration. Among 56 patients, 16 had LF-SAS (29%), and 40 had NF-SAS (71%). Severe adverse clinical events were not observed 48 h after tolvaptan administration. In both groups, the urine volume significantly increased after tolvaptan administration in comparison to 24 h before tolvaptan administration (both, p < 0.01). There were no changes in the urine volume during the initial 24 and 48 h. In the LF-SAS group, tolvaptan resulted in a significant decrease in fluid balance during the initial 24 and 48 h compared to 24 h before tolvaptan administration (p < 0.05). Adding tolvaptan to conventional treatment is safe and effective without renal dysfunction and hypotension in patients with SAS, including those with LF.

Body Surface Radiation Exposure in Interventional Echocardiographers During Structural Heart Disease Procedures.

Background: The distribution of radiation exposure on the body surface of interventional echocardiographers during structural heart disease (SHD) procedures is unclear. Objectives: This study estimated and visualized radiation exposure on the body surface of interventional echocardiographers performing transesophageal echocardiography by computer simulations and real-life measurements of radiation exposure during SHD procedures. Methods: A Monte Carlo simulation was performed to clarify the absorbed dose distribution of radiation on the body surface of interventional echocardiographers. The real-life radiation exposure was measured during 79 consecutive procedures (44 transcatheter edge-to-edge repairs of the mitral valve and 35 transcatheter aortic valve replacements [TAVRs]). Results: The simulation demonstrated high-dose exposure areas (>20 µGy/h) in the right half of the body, especially the waist and lower body, in all fluoroscopic directions caused by scattered radiation from the bottom edge of the patient bed. High-dose exposure occurred when obtaining posterior-anterior and cusp-overlap views. The real-life exposure measurements were consistent with the simulation estimates: interventional echocardiographers were more exposed to radiation at their waist in transcatheter edge-to-edge repair than in TAVR procedures (median 0.334 µSv/mGy vs 0.053 µSv/mGy; P < 0.001) and in TAVR with self-expanding valves than in those with balloon-expandable valves (median 0.067 µSv/mGy vs 0.039 µSv/mGy; P < 0.01) when the posterior-anterior or the right anterior oblique angle fluoroscopic directions were used. Conclusions: During SHD procedures, the right waist and lower body of interventional echocardiographers were exposed to high radiation doses. Exposure dose varied between different C-arm projections. Interventional echocardiographers, especially young women, should be educated regarding radiation exposure during these procedures. (The development of radiation protection shield for catheter-based treatment of structural heart disease [for echocardiologists and anesthesiologists]; UMIN000046478).

Surfactant protein D: a useful marker for differentiation of drug-induced pneumonia and bacterial pneumonia.

BACKGROUND: Drug-induced pneumonia (d-pneumonia) and bacterial pneumonia (b-pneumonia) are often difficult to differentiate; therefore, this study examined the possibility of differentiating them using serum biomarkers. METHODS: The study included 22 and 16 patients diagnosed with b- and d-pneumonia, respectively, at our institution or affiliated institutions. For d-pneumonia, the causative drug was minocycline hydrochloride in four patients, gefitinib in two patients, nivolumab in two patients, pembrolizumab in two patients, sulfasalazine in two patients, loxoprofen in one patient, Bouiougitou in one patient, edoxaban tosilate hydrate in one patient, and abemaciclib in one patient. White blood cell (WBC), C-reactive protein (CRP), Krebs von den Lungen-6 (KL-6), surfactant protein (SP)-D, and SP-A levels were measured in each patient and compared between the groups. RESULTS: Significant differences were noted in the WBC and SP-D levels between the two groups (P < 0.05, P < 0.001), but not in the CRP, KL-6, or SP-A levels. CONCLUSION: The study results suggest that SP-D is a useful marker for differentiating b-pneumonia and d-pneumonia.

The clinical characteristics and prognosis of lesions with in-stent eccentric tissue proliferation and strong signal attenuation detected by optical coherence tomography.

There are still some patients who require repeat revascularization despite of drug-eluting stent (DES) implantation. The present study aimed to investigate the relationship between optical coherence tomography (OCT) findings and recurring target lesion revascularization (TLR) after percutaneous coronary intervention (PCI) for in-stent restenosis (ISR). We reviewed 50 patients (54 coronary lesions) who underwent PCI for ISR, which included 25 DES-ISR lesions. The PCI strategy depended on the interventionalist's discretion, and DES implantation was performed for 38 (70 %) lesions. Tissue characteristics were assessed qualitatively and quantitatively using the frame showing maximal lumen narrowing (minimal lumen area). In qualitative analysis, OCT detected coexistence of eccentric tissue proliferation and strong signal attenuation (ESA). ESA was observed in six lesions (11 %) in five patients (10 %). Hemodialysis (80 vs. 20 %, p = 0.013) and DES-ISR (100 vs. 40 %, p = 0.0069) were significantly more frequent in ESA patients/lesions than in others. One-year follow-up revealed that re-TLR was more frequently performed for ESA lesions (83 vs. 8 %, p = 0.0002). The findings reveal that ESA detected in OCT images of ISR is related to TLR after PCI for DES-ISR especially in patients undergoing maintenance hemodialysis.